ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2446C>T (p.Arg816Ter) (rs886041347)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000376782 SCV000329837 pathogenic not provided 2018-03-05 criteria provided, single submitter clinical testing The R816X nonsense variant in the NF1 gene has been reported previously in association with neurofibromatosis type 1 (Bahuau et al., 1998; Fahsold et al., 2000; Ko et al., 2013). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we consider this variant to be pathogenic.
Ambry Genetics RCV000492291 SCV000581352 pathogenic Hereditary cancer-predisposing syndrome 2016-09-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Strong segregation with disease (lod >3 = >10 meioses)
Invitae RCV000497042 SCV000628443 pathogenic Neurofibromatosis, type 1 2018-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg816*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with neurofibromatosis type 1 (NF1) (PMID: 9150739, 18484666, 15146469, 23668869, 10712197) and in a family with neurofibromatosis–Noonan syndrome (PMID: 9475595). It has been also reported in an individual with NF1 and malignant peripheral nerve sheath tumor (PMID: 19142971) and in an individual with NF1 and pheochromocytoma (PMID: 25403449). ClinVar contains an entry for this variant (Variation ID: 280055). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626642 SCV000747344 pathogenic Multiple cafe-au-lait spots; Axillary freckling; Large cafe-au-lait macules with irregular margins; Lisch nodules; Delayed fine motor development; Inguinal freckling 2017-01-01 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000497042 SCV000781952 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762986 SCV000893431 pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000376782 SCV000927362 pathogenic not provided 2017-07-31 criteria provided, single submitter clinical testing
Medical Genetics,University of Parma RCV000497042 SCV000588746 likely pathogenic Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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